OBJECTIVE: Phosphoinositide 3-kinase (PI3K) is required for murine adipocyte differentiation. However, a recent report concluded that PI3K was not involved in the differentiation of human preadipocytes into adipocytes. We have re-examined the role of PI3K in human preadipocyte differentiation, enrolling more patients and using more adipogenic indices. METHODS: Human preadipocytes, isolated from nine patients, were induced to differentiate in the presence or absence of 100 nM wortmannin. After 12-15 days, triacylglycerol accumulation and the expression of adipogenic markers ( fatty acid synthase and adiponectin) were measured. RESULTS: A significant inhibition in triacylglycerol accumulation and in the induction of fatty acid synthase protein expression was observed, but there was no effect on adiponectin protein expression. CONCLUSION: Inhibition of PI3K reduces the differentiation of human preadipocytes into adipocytes, suggesting a role for this enzyme in the human adipogenic process.