The effects of bezafibrate and fenofibrate on serum lipoproteins and serum urinary uric acid were compared. In a double-blind, placebo-controlled, cross-over study, each drug was administered in random order for 6 weeks followed by a 3-week drug-free phase to ten men with primary hypertriglyceridemia. Serum triglyceride and cholesterol concentrations decreased significantly with both fenofibrate and bezafibrate, although no significant change in serum apolipoprotein B, serum low density lipoprotein (LDL) cholesterol or serum high density lipoprotein (HDL) cholesterol concentrations was apparent. Serum uric acid levels, which were elevated on placebo and bezafibrate, were significantly reduced by 20% by fenofibrate. This was associated with an increase in renal uric acid clearance of 30% during fenofibrate therapy. Because it seems likely that hypertriglyceridemia and hyperuricemia are linked by a common carbohydrate inducibility, we studied the acute hyperuricemic response to orally administered fructose. Fructose (50 g) caused the anticipated rise in serum urate reaching a peak between 60 and 90 minutes, which was quantitatively greater in the men with hypertriglyceridemia than in healthy controls. The serum uric response to fructose was unaffected by bezafibrate, but was converted to normal by fenofibrate. The hyperuricemic action of fenofibrate is of sufficient magnitude to be of therapeutic value in the management of patients whose hypertriglyceridemia is associated with gout.