We conducted an immunohistological investigation on the pathogenesis of interstitial foam cell formation in patients with idiopathic membranous nephropathy (MN). The patients were divided into two groups: Group I consisted of 23 MN patients with interstitial foam cells; Group II consisted of the other 159 patients without foam cells. Age at renal biopsy, duration of proteinuria, blood pressure and other clinical parameters were not significantly different between the two groups. The proportion of nephrotic patients in Group I was 52.2% (12/23), and was not significantly different from that in Group II (48.4%, 77/159). Renal biopsy specimens were examined by immunoperoxidase studies using monoclonal antibodies. The interstitial foam cells were positive for EBM11 (CD68) and 25F9, which are markers of macrophage (M phi) and mature M phi, respectively, but did not express markers of T cells. In interstitial infiltrating cells, both M phi and T cells were observed, but mature M phi were seldom seen. Furthermore, LFA-1 and ICAM-1, but not ICAM-3 (the third ligand for LFA-1) were observed in the interstitial foam cells. LFA-1 and ICAM-3 were observed mainly in interstitial infiltrating cells, but ICAM-1 was observed to a much lesser extent in these cells. These results suggest that interstitial foam cells in MN may be independent of severe hyperlipidemia and proteinuria, and that there may be different mechanisms underlying the accumulation of interstitial foam cells and infiltrating m phi s. Further investigations are required to clarify the pathogenesis of interstitial foam cells in renal tissue.