Lipogenesis from different substrates was determined in isolated human sebaceous glands after 17-20 h in culture. Rates of total lipogenesis were 1O03 +/- 141, 842 +/- 90, 481 +/- 57 pmol.h - 1 .gland - 1 +/- SE from acetate, lactate and glucose, respectively, when present as sole substrates: the rate from glucose was significantly lower (P < 0.01). Squalene synthesis was greatest from acetate at 479 +/- 44 pmol.h - 1 .gland - 1 ; significantly higher than from lactate (281 +/- 45 pmol.h - 1 .gland - 1 ) or glucose at 119 +/- 18 pmol.h - 1 .gland - 1 . Wax ester plus cholesterol ester synthesis showed similar dependence on substrate but triglyceride synthesis was unaffected. We conclude that the added substrate determines both the rate and pattern of non-polar lipid synthesized by isolated human sebaceous glands.