Sixteen children (7 boys and 9 girls, aged 1.9 to 14.8 years) diagnosed with acute tubulointerstitial nephritis [ATIN: 4 drug-induced, 6 infection, 2 tubulointerstitial nephritis and uveitis syndrome (TINU), and 4 unclassified] were studied to characterize the nature of the interstitial mononuclear cells involved in each clinical picture of the disease Six children with asymptomatic microscopic hematuria whose histology was a minimal change in renal biopsy were studied as controls. The enzyme immunoassay was carried out using the biopsy specimen obtained from 4 to 42 days after the onset of illness. In ATIN, the number of renal interstitial infiltrating CD3, CD4, and CD8 T lymphocytes, respectively, was significant larger than that in the minimal change kidneys [CD3 T cells; median 94 (range 3.2-330)/mm2 interstitial area vs. median 7.8 (range 1.1-23), p = 0.003, CD4 T cells; 11 (range 0.5-78) vs. 1.5 (range 0-7.7), p = 0.018, CD8 T cells; 22 (range 1.0-150) vs. 2.9 (range 0-14), p = 0.047]. In addition, a positive correlation was found between the CD3 and CD4 T cells. On the other hand, in regard to the relationship between the CD3 and CD8 T cells, CD8/CD3 was extremely low in 3 cases in the infection-induced group, but the other 3 groups included no extremely low CD8/CD3 cases. Although interstitial monocytes/macrophages were smaller than the T lymphocytes in number, a positive correlation was revealed between the T lymphocytes and monocytes/macrophages (CD3 T cells vs. monocytes/macrophages; r = 0.53, p = 0.039). No relationship was found between the duration from the onset of illness to renal biopsy and mononuclear cell involvement. These findings suggest that cellular immunity, mainly T lymphocytes, may play a role in the pathogenesis of ATIN in children.