Differentiation antigens of T and B lymphocytes were sought in human fetal and adult kidney tissues with monoclonal antibodies by indirect immunofluorescence. Antibodies that identify B cells (BA-1 and anti-B1) and leukemia-associated antigens (BA-2, BA-3, and J5) reacted with renal glomerular and tubular epithelium at characteristic stages of nephron development. BA-1 and BA-2 identified primitive epithelium of the glomerulus, and ureteral bud and nephron development was characterized by loss of BA-1 and BA-2 binding by visceral glomerular and proximal tubular epithelium. In contrast, J5 and BA-3 did not react with primitive epithelium but identified visceral and proximal tubular epithelium after appearance of the glomerular basement membrane and throughout subsequent nephron differentiation. Anti-B1 reacted with ureteral bud and distal nephron epithelium in more mature fetal tissues. Monoclonal antibodies that identify populations of T cells and thymocytes did not react with parenchymal cells of fetal or adult kidneys. They did identify interstitial mononuclear cells whose size and relative numbers appeared gestationally related. Monoclonal antibodies that recognize a human monomorphic HLA-DR determinant reacted with glomerular and peritubular capillaries as early as 11 wk of gestation. The distribution and density of HLA-DR expression appeared more related to gestation than nephron development. The relationship between renal parenchymal expression of lymphohemopoietic antigens and glomerular acquisition of C3b receptor activity was determined using C3b-coated fluoresceinated Escherichia coli. In fetal tissues, C3b receptor activity appeared developmentally related to the loss of determinants recognized by BA-1 and BA-2 and to the appearance of J5 and BA-3 reactivity with visceral glomerular epithelium. Tissue binding and comparative avidity of J5 and BA-3 antibodies was studied in a series of experiments, the results of which suggest that these antibodies are directed against the same epitope or closely related epitopes of the common acute lymphoblastic leukemia antigen. The common expression of differentiation antigens and C3b receptors by cells of lymphohemopoietic lineage and renal epithelia suggests the possibility of heretofore unrecognized commonality of function or developmental experience.