This study is concerned with the detectionof overt and latent viruses in explant cultures of renal biopsies from 72 patients with various forms of renal disease. Of the 77 biopsies, 52 grew in culture and five of these developed vacuolization, multinucleated syncytia, or cytoplasmic granules. None of these five patients had evidence of streptococcal involvement. Four had focal or diffuse proliferative glomerular changes in the renal biopsy and three of these had nephrotic syndrome. The two most interesting cases included one patient with hypocomplementemic mesangioproliferative glomerulonephritis and another patient with presumptive evidence of systemic lupus erythematosus. Cultures of the first patient thrived for 6 months and persistently showed vacuolization. Cultures of the second patient developed multinucleated and vacuolated cells and these changes reappeared after passage with supernatant of the original culture. This study confirms the absence of overt viruses in renal biopsy cultures. Although the significance of vacuolated and multinucleated cells in these cultures is at present not clear, such changes are suggestive of the presence of a cytopathic agent.