Human renal tubular cells derived from nephrectomy specimens were maintained in culture and grown to confluence. Immunocytochemistry, using a panel of antibodies selected for their ability to bind to different cell types within the nephron, showed the cells to be predominantly of epithelial origin with no significant contamination by fibroblasts or cells of endothelial origin. Ten to thirty percent of the cells expressed the putative distal marker, epithelial membrane antigen (EMA), a finding confirmed by flow cytometry. Cells expressing EMA were positively selected from mixed cultures by magnetic activated cell sorting (MACS). Kallikrein activity, expressed as mU/10(6) cells, in the EMA +ve cells, was increased fourfold to sixfold when compared with that in the EMA -ve cells. Cultures of characterized human renal tubular cells and sub-populations enriched with distal cells should prove useful in studies of synthesis and release of parameters of the kallikrein kinin system (KKS) to physiological stimuli. Furthermore, a better understanding of the toxic effect on the KKS of clinically useful drugs, particularly those used for immunosuppression, may lead to therapeutic interventions to lessen unwanted effects.