Recent animal work suggests that gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) enhance calcium absorption, reduce excretion and increase calcium deposition in bone. A pilot study was set up to test the interactions between calcium and GLA + EPA in humans. Sixty-five women (mean age 79.5), taking a background diet low in calcium, were randomly assigned to GLA + EPA or coconut oil placebo capsules; in addition, all received 600 mg/day calcium as the carbonate. Markers of bone formation/degradation and bone mineral density (BMD) were measured at baseline, 6, 12 and 18 months. Twenty-one patients were continued on treatment for a second period of 18 months, after which BMD (36 months) was measured. At 18 months, osteocalcin and deoxypyridinoline levels fell significantly in both groups, indicating a decrease in bone turnover, whereas bone specific alkaline phosphatase rose indicating beneficial effects of calcium given to all the patients. Lumbar and femoral BMD, in contrast, showed different effects in the two groups. Over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2% in the placebo group. Femoral bone density increased 1.3% in the treatment group, but decreased 2.1% in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1% in patients who remained on active treatment, and 2.3% in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7%. This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients, and that they are safe to administer for prolonged periods of time.