Leukocyte analysis using monoclonal antibodies in human glomerulonephritis. The leukocyte subpopulations were analyzed within both the glomeruli and the interstitium in renal biopsies from 145 patients with various forms of glomerulonephritis. Cells were identified by monoclonal antibodies to leukocyte cell–surface antigens and immunoper-oxidase labelling. Leukocytes, as defined by a monoclonal antibody to the leukocyte common antigen (PHM1), were present in normal, human renal tissue in both glomeruli (2.8 ± 0.6 cells/glom. cross section) and interstitium (102 ± 18 cells/mm²). Monocytes constituted the predominant infiltrating cell type in normal glomeruli (1.3 ± 0.2) and T cells were rarely found (0.3: range 0 to 0.8), whereas both monocytes (34 ± 10/mm²) and T lymphocytes (33 ± 14/mm²) were found in the normal interstitium. In the non-proliferative forms of glomerulonephritis there was no significant increase in the number of glomerular inflammatory cells when compared with normal glomeruli. However, significantly increased numbers of T lymphocytes were seen in the interstitium of biopsies with minor non-specific changes (67 ± 15/mm²), membranous nephropathy (134 ± 30/mm²), focal glomerulosclerosis (207 ± 53/mm²), and diabetic nephropathy (198 ± 81/mm²). In the proliferative forms of glomerulonephritis only crescentic GN and post-infectious GN demonstrated significantly-increased glomerular monocytes and granulocytes. There was no significant increase in the number of glomerular T cells when compared with normal glomeruli. However, there was a significant increase in the number of interstitial T lymphocytes in all forms of proliferative glomerulonephritis when compared with the normal interstitial cell population. In particular, this was seen in post-infectious GN (183 ± 49/mm²), IgA nephropathy (283 ± 59/mm²), diffuse mesangial proliferative lupus nephritis (215 ± 64/mm²), crescentic GN (508 ± 101/mm²), membrano-proliferative GN (481 + 127/mm²) and focal proliferative GN (289 ± 92/mm²). There was no significant difference in the OKT4:OKT8 ratio compared with that in the normal interstitium. There was a weak negative correlation only between glomerular leukocyte accumulation and renal function (as measured by creatinine clearance) (r = 0.27, P < 0.01), whereas there was a strong correlation between interstitial leukocyte accumulation and decline in creatinine clearance (r = -0.61; P < 0.001). This study demonstrates and characterizes the interstitial leukocytic infiltrate, predominantly T lymphocyte, in human glomerulonephritis and shows a strong correlation with impairment of renal function.