Since increased mesangial accumulation of matrix has been considered to be an important event in the development of focal glomerulosclerosis, we investigated whether morphine, an active metabolite of heroin, can modulate mesangial accumulation of immune complexes. Control or morphine-dependent rats were administered intraperitoneal ferritin (8 mg/100 g body weight) daily for 6 weeks. Body weight, blood pressure, serum creatinine, 24-hour urinary protein and creatinine excretion rates were measured at 3-week intervals. Rats were sacrificed at the end of 6 weeks and kidney tissue was studied by light, immunofluorescence and electron microscopy. Serum creatinine levels and urinary protein excretion rates were not different between control and morphine-dependent rats. All morphine-dependent rats developed hematuria, whereas only 1 control rat developed hematuria. Light microscopy revealed no proliferation of mesangial cells and only a minimal increase in the mesangial matrix. Electron-microscopic studies showed deposition of immune complexes in the mesangial region. Mesangial cells showed aggregation of ferritin in lysosomes. Immunofluorescence studies revealed the presence of IgG staining predominantly in the mesangial region. The majority (60%) of morphine-dependent rats showed a diffuse mesangial deposition of IgG when compared to control rats (83%) who showed only focal deposition. These results indicate that morphine enhances deposition of immune complexes in the mesangium. Morphine-induced matrix but may also change its quality. This may play a pathogenic role in the development of glomerular lesions in patients who abuse opiates.