Management-induced degradation of soil chemical and microbial quality is one of the most pressing concerns and a considerable threat to the sustainability of agroecosystems. However, information on this important issue is limited and largely based on short-term studies. A long-term experiment initiated in 1939 at the University of Pretoria provided a unique opportunity to assess the direct and residual effects of manure and inorganic fertilizers on soil chemical properties, microbial components and maize yield in rotation with field pea. Long-term addition of manure resulted in increased total organic C (TO C), total Nand available P levels in the soil. Seasonally, these nutrients exhibited variations that appeared to be related to influences of crop rotation. Soil N content in an adjacent native site remained relatively constant but tended to increase in the control and manured plots. Soil microbial biomass C, Nand P and microbial populations were affected by previous manure application as well as by crop rotation. Microbial biomass and numbers were generally higher in the manured plots. Manure application also had substantial residual effects and resulted in maize grain yields higher than in the control. Long-term NPK application resulted in decreased TOC and basic cation contents, and lowering of soil pH. The decrease in TOC was greater in single fertilizer treatments whereas basic cation contents and pH declined more in the balanced fertilizer treatments. Soil microbial biomass and numbers were influenced by, and exhibited qualitative changes in response to, long-term fertilization. Crop rotation also exerted effects on chemical and microbial properties of the soil. Maize grain yield showed significant increases in response to balanced fertilizer treatments. Response of maize to simple fertilizer applications was not beneficial in terms of yield returns. These results suggest that judicious use of inorganic fertilizers may, in the long-term, maintain soil quality and productive capacity. A comparison of the effects of residual manure and NPK fertilizers on the content of selected nutrients, microbial properties, C and N inputs, tissue nutrient concentration and crop yield showed differences due to treatments. TOC, total N and available P levels were increased due to residual manure alone or in combination with NPK fertilizers. C and N inputs and tissue P concentration were also generally higher in manured than in the NPK treatment. However, the higher increase in nutrient contents of manured plots was not reflected in microbial properties of the soil. Despite lower nutrient levels, the NPK treatment resulted in relatively greater increases in microbial properties of the soil. The differential responses were largely due to differences in quality and decomposability of organic material. Organic material in the NPK treatment appeared to have a higher decomposition and turnover rate than in other treatments, suggesting that C limitation in soils of low C but good nutrient supply may be compensated by high turnover rates of the available organic materials. The beneficial effect of residual manure on microbial properties and crop yield was decreased by application of supplemental N fertilizer but remained unaffected by application of supplemental K fertilizer. The depressive effect of excess soil P levels on soil microbial properties and crop yield was exacerbated by supplemental N fertilizer and mitigated by supplemental manure and K fertilizer applied to residual P. The decrease in available P levels due to supplemental K application implies that this may serve as a viable alternative to ameliorate soils with excess P levels.