Mononuclear inflammatory cells were studied using monoclonal antibodies in the interstitium and glomeruli of 35 renal biopsy specimens from patients with lupus nephritis already taking immunosuppressants. The aims of this study were to assess the composition and significance of the infiltrate, and to assess correlations with immediate glomerular function and ability to predict the future course of the disease. The majority of interstitial cells were T lymphocytes and monocytes/macrophages. The number of interstitial CD4 + ve T helper/inducer lymphocytes was greater than that of CD8 + ve T cytotoxic/suppressor cells in only 19 out of 35 biopsies, the mean CD4:CD8 ratio being only 1.5 +/- 1.2. NK cells and B lymphocytes were a minor component only. Some expression of IL-2, transferrin and C3b receptors was seen on interstitial cells, but HLA-DR expressing cells were much in excess of controls and the numbers of tubular cells expressing HLA-DR was also increased. The number of interstitial T cells, CD4 + ve cells and monocytes/macrophages was highly correlated with the extent of chronic damage judged by optical microscopy. There was also an association between glomerular function at biopsy and numbers of interstitial T cells, CD8 + ve cells, monocytes/macrophages and DR expressing cells. Subsequent decline in renal function, however, was associated only with numbers of monocytes/macrophages and the rather small number of C3b receptor-positive cells. The presence of tubulointerstitial immune aggregates of Ig and/or C in 63% of patients was associated with greater numbers of NK cells. As previously described, the degree of renal function at biopsy correlated with a chronicity index based on optical microscopy. No correlations were found between numbers or types (mostly monocyte/macrophages) of intraglomerular leukocytes and clinical or biopsy features, except that more proliferative types showed greater leukocyte numbers. One hypothesis consistent with our findings is that interstitial T cells and monocytes may be important determinants of pathogenesis and progression of lupus nephritis. While several mechanisms may play an initial role, interstitial monocytes may be the major factor in chronic injury.