Essential fatty acid deficient animals develop osteoporosis. Eicosapentaenoic acid and gamma-linoleic acid have been reported to have positive effects on bone metabolism in both the growing male rat and the ovariectomized (OVX) female rat. These effects have been further investigated using a novel gammalinolenic/eicosapentaenoic acid diester together with an oestrogen implant in the ovariectomized, female Sprague Dawley rat. Rats were sham-operated or ovariectomized at age 11 weeks. Two groups of OVX rats received an oestrogen implant at ovariectomy. Animals received fatty acids, linoleic acid (control) or a diester with gamma-linolenic acid and eicosapentaenoic acid as part of a semi-synthetic diet. Bone calcium content and excretion of deoxypyridinolines as marker of bone degradation were measured at 14 weeks. Oestrogen, as well as diester alone, increased calcium/femur to sham levels. Oestrogen plus diester potentiated the effect of oestrogen on bone calcium (P< 0.05 vs OVX). At the same time, oestrogen alone and the combination of oestrogen plus diester significantly reduced (P < 0.05 vs OVX) urinary deoxypyridinoline and hydroxyproline excretion. Again, the diester potentiated the effect of oestrogen. The effects of the diester alone, together with the potentiated effects of oestrogen by the essential fatty acids on osteoporosis, are novel findings. (C) 1999 Harcourt Publishers Ltd.