Following a small dose of nephrotoxic serum (NTS) WKY rats demonstrated crescentic glomerulonephritis, which was characterized by the early infiltration of CD8 positive cells in glomeruli. In vivo depletion of CD8 positive cells from WKY rats completely prevented proteinuria (4.6 +/- 4.8 mg/day vs. 105.3 +/- 11.6 mg/day on day 10; N = 19, P less than 0.001) and crescent formation (2.7 +/- 2.9% vs. 94.3 +/- 2.6%; P less than 0.001). Immunofluorescence revealed complete inhibition of the influx of CD8 positive cells and subsequent reduction of the infiltration of macrophages in the glomeruli. Glomerular binding of 125I-anti-rat glomerular basement membrane antibodies, host anti-rabbit IgG production and the C3 level in the circulation were the same as in the control. These data indicate that CD8 positive cells play a key role in glomerular injury and crescent formation. This model provides a useful system for studying the cellular mechanisms that lead to glomerular injury and subsequent crescent formation.