The effects of two phosphodiesterase inhibitors, e.g. theophylline and D-4-(3-butoxy-4 methoxybenzyl)-2-imidazolidinone (RO-20-1724) on the antilipolytic action of insulin in human adipocytes were investigated. At a concentration of 1 mmol/l (theophylline) and 0.1 mmol/l (RO-20-1724) both inhibitors increased cyclic AMP to a similar extent. However, their effects on insulin action were different. Whereas addition of theophylline abolished the ability of insulin to inhibit lipolysis, insulin was fully functional in depressing glycerol release in the presence of RO-20-1724. The results suggest that the insulin-sensitive phosphodiesterase of human adipocytes may be relatively resistant to RO-20-1724 as has been shown for the enzyme system of 3T3-L1 adipocytes.