The present pilot study investigated the effect of long-term treatment with picotamide on baseline and exercise-induced urinary albumin excretion levels in normotensive patients with type II diabetes mellitus. Six patients with type II diabetes were studied: four patients (two men and two women; mean age, 52 +/- 11 years) were treated for 9 months with picotamide (300 mg, TID) and two patients who did not receive the study medication served as controls. Three of the picotamide-treated patients were given a cycloergometric exercise test at baseline and after 3 and 6 months of therapy to evaluate the effects of the drug on exercise-induced microalbuminuria. Microalbuminuria at rest was measured in all patients at baseline and after 3, 6, and 9 months. At the end of the study, all the picotamide-treated patients demonstrated a significant decrease in microalbuminuria at rest (from 41.7 +/- 12.7 micrograms/min at baseline to 11.8 +/- 3 micrograms/min after 9 months) and after exercise (peak at baseline 103 +/- 36 micrograms/min vs 65.8 +/- 11 micrograms/min after 6 months). Conversely, in the two controls, microalbuminuria at rest increased from 45.1 +/- 0.9 micrograms/min at baseline to 151 +/- 59 micrograms/min at the end of the 9-month study period. (All values given as mean +/- SEM.) In conclusion, long-term administration of picotamide was effective in reducing abnormal exercise-induced microalbuminuria and albuminuria at rest. These findings suggest that long-term treatment with picotamide of normotensive patients with type II diabetes mellitus and incipient nephropathy may slow the progression of the nephropathy in its early stages.