To investigate the relationship between polyunsaturated fatty acid (PUFA) and bone metabolism in renal transplant patients, plasma phospholipid (PP) PUFA levels, biochemical markers of bone turnover and bone mineral density (BMD) were determined in 22 recipients of a first renal allograft at baseline and after a mean 24.4 month follow-up. A significant increase in PP n-3 PUFA content, in the [n-3 PUFA/ arachidonic acid] ratio and in BMD values was observed, as well as a close correlation between the increase in PP n-3 PUFA content and femoral neck BMD. Multivariate regression analysis showed that BMD improvement was positively related to PP n-3 PUFA variation and baseline PP eicosapentaenoic acid levels, and negatively to PP arachidonic acid modification. Tacrolimus- versus cyclosporine-treated patients demonstrated a significant increase in femoral neck BMD and PP n-3 PUFA content. This is the first longitudinal study showing a link between PP-PUFA composition and bone disease in renal transplantation.