The effects of the non-steroidal anti-inflammatory drug diclofenac and the pyrazolone derivative dipyrone on renal function were compared with those of placebo in 12 healthy male volunteers in a randomized, controlled, triple-crossover study with a wash-out period of 4 days between each of the 3 trial periods (dipyrone, diclofenac and placebo) which lasted three days each. The volunteers received dipyrone (1 g, 3 times/day for 2 days, followed by twice 1 g on the main trial day, which was day 3 of each study period) or diclofenac (50 mg, 3 times/day for 2 days, followed by twice 50 mg on the main trial day) or placebo orally. Standardized meals (50 mEq sodium per day) were given from one week before the start until the end of the study and on the main trial days a protein-rich lunch (2 g protein/kg body weight) was taken. Renal function was assessed in each study period by measurement of creatinine-clearance, inulin-clearance and p-aminohippurate (PAH)-clearance to characterize glomerular filtration rate and renal plasma flow. High protein intake induced glomerular hyperfiltration (increased creatinine-clearance, inulin-clearance and PAH-clearance) in all 3 study periods (dipyrone, diclofenac, placebo). Dipyrone and diclofenac had no effect on renal clearance of creatinine, inulin or PAH in comparison to placebo. These results show that dipyrone and diclofenac at therapeutic dosages over 3 days do not decrease glomerular filtration and renal plasma flow in healthy individuals. Furthermore, it is unlikely that prostaglandins play a major role in protein-induced glomerular hyperfiltration.