The relation of plasma levels of prostaglandins to the occurrence of flushing induced by niceritrol was investigated. Niceritrol increased plasma levels of PGE2 (p less than 0.01) and 6 keto-PGF1 alpha (p less than 0.05) in 10 male subjects and aspirin reduced the level of PGE2 (p less than 0.01). Five of 10 subjects had flushing, and aspirin reduced flushing in 4 subjects. On the basis of the above study, we treated 35 hyperlipidemic patients with niceritrol in combination with aspirin, investigating the effect of the treatment of serum lipids and postheparin lipolytic activity. None of the 12 cases given aspirin from the start of the treatment experienced flushing, whereas 9 of the 23 cases not given aspirin experienced flushing, which was suppressed by adding aspirin in prescription in all cases except one. Niceritrol decreased serum cholesterol, triglyceride and atherogenic index. It also increased HDL2 cholesterol and decreased HDL3 cholesterol. The LPL activity in postheparin plasma increased in all cases after niceritrol treatment. In conclusion, aspirin increased compliance of niceritrol by reducing the occurrence of flushing probably due to the decreased levels of prostaglandins, yielding favorable results for the long-term treatment of hyperlipidemia with a sufficient doses of niceritrol.