Populations of mononuclear inflammatory cells infiltrating the renal interstitium in LN were studied by means of an avidin-biotin immunoperoxidase technique applied to cryostat sections of 26 renal biopsies (3 WHO class IIb; 4 class III; 8 class IV; 4 class V; 4 class III and V; and 3 class IV and V). The majority of interstitial leukocytes were T cells (mean 65.7 +/- 14.1). The number of cells reactive with OKT8 (47.3 +/- 11.0) exceeded the number of OKT4 positive cells (32.5 +/- 11.3) in 22 of 26 biopsies. Cells reactive with antimonocyte antibodies OKM1 and OKM5 (6.7 +/- 5.9 and 7.9 +/- 5.9, respectively) and B lymphocytes (OKB2 3.9 +/- 3.5) were a minor component of the interstitial infiltrates. Monocytes were the predominant cell type among stained cells in glomerular tufts and crescents. Tissue T4/T8 ratios varied widely (range 0.31 to 1.81), and were less than 1 in 22 of 26 patients. There was no correlation between tissue T4/T8 ratios and simultaneous peripheral blood T4/T8 ratios. Using stepwise multivariate linear regression, tissue T4/T8 ratio was found to correlate highly with renal histologic activity (P less than 0.001) but was not independently predictive of any other histopathologic or clinical variable studied. Mean tissue T4/T8 ratio in LN was significantly lower than that of other glomerular and interstitial diseases studied (P less than 0.001), a finding which may reflect differences in the pathogenesis of renal injury. These findings suggest that local cellular immune mechanisms may be important in the modulation of disease activity in LN.