Colchicine was given to rats in the heterologous phase of passive Heymann nephritis to see whether this drug could reduce proteinuria. Treatment with 0.06 mg/day for 14 days caused significant reductions in proteinuria and albuminuria. Administration of dimethyl sulfoxide (DMSO) alone or in combination with colchicine also reduced protein and albumin excretion. In a long-term experiment, rats treated with colchicine had significantly less proteinuria. After stopping therapy, urine protein excretion was similar to controls. No differences in glomerular C3 and IgG deposition were found between treated and control rats 24 h, 3,7 and 14 days after immunization. Depressed serum C3 levels were measured at 24 h in colchicine-treated rats. No difference in serum-circulating immune complexes was detected between the two groups. Concurrent administration of indomethacin and colchicine to rats with passive Heymann nephritis (PHN) partially reversed the reduction in proteinuria and albuminuria seen in rats treated with colchicine alone. The G.F.R, however, was significantly reduced in colchicine-treated rats as well as in rats treated with colchicine and indomethacin. Serum cholesterol and triglyceride levels were significantly lower in colchicine-treated rats than in controls. Serum cholesterol concentrations in rats given both colchicine and indomethacin were similar to control values. These findings suggest that colchicine reduces urine protein and albumin excretion, and hyperlipidemia in PHN. The finding that indomethacin partially blocks the effects of colchicine suggests that renal prostaglandin stimulation by colchicine may have been involved in the reduction in proteinuria.