The aim of the study was to investigate the association between depression and low bone mineral density (BMD) in premenopausal females. The rationale for the study was that depression is often characterized by cortisol hypersecretion. The role of cortisol includes effects on bone metabolism and the immune system: cortisol is a bone resorption agonist through its support of osteoclastogenesis. The release of pro-inflammatory cytokines, (especially IL-1, IL-6 and TNF-alpha) which induce cortisol secretion, also pushes the balance of bone remodelling in favour of resorption, consequently causing loss of bone mineral density. Significant results have been reported in studies of various groups across the USA, Europe and Asia, indicating a causal role for depression in osteoporosis. However, some studies could not support this association. With both osteoporosis and depression representing growing public health concerns in South Africa, the aim of this study was to examine the association between depression and loss of BMD in a South African sample with varying levels of depression. The study was approached from two starting points: the first used low BMD as the departure point and the second was undertaken from the diagnosis of depression. This was achieved by first investigating women where the primary concern was possible low BMD (referred to as Study 1) and secondly by assessing women whose primary diagnosis was clinically confirmed major depression (Study 2). Study 1 involved investigation of BMD in a volunteer-based sample of 40 premenopausal women drawn from three different sources. All volunteers underwent a DEXA scan, were assessed for depression and supplied saliva for cortisol analysis. Study 2 examined the BMD of five psychiatric patients diagnosed with severe, recurrent major depression and four healthy controls. These volunteers were required to undergo the same testing as subjects in Study 1. In addition, blood and urine samples were taken to examine bone turnover markers (bone specific alkaline phosphate, osteocalcin, urine pyridinoline cross-linked C-telopeptide and deoxypyridinoline). The pro-inflammatory status of the psychiatric patients was compared to reference ranges. The latter served as a small exploratory study and an introduction to further avenues of research. Study 1 revealed no clear general association between depression and bone density on DEXA scores. However, a correlation was found between left femoral neck BMD and depression in those women with low BMD only. Significant differences were found though between subjects with normal and low BMD in terms of body mass index (BMI) and contraception use. Study 2 on the other hand, indicated a trend of association between depression and low BMD: subjects suffering with severe major depression were noted to have lower bone density (on DEXA) and higher bone turnover (as measured by markers of bone turnover) as well as higher cortisol levels than healthy controls. In addition, depressed subjects exhibited elevated IL-1-alpha levels but normal TNF-alpha levels when compared to normative data. In conclusion, the study indicated that the effect of depression on bone density is dependent on the intensity and duration of depression. IL-1-alpha and cortisol may be instrumental in this loss of BMD.