The possible human nephrotoxicity of silica has often been suggested by previous anecdotal reports and uncontrolled clinical studies of silicotic patients. Urinary excretions of albumin, alpha-1-microglobulin (AMG), and beta-N-acetyl-glucosaminidase (NAG) were measured in 33 male workers exposed to silica (mean duration of employment 16 years) and 19 male age matched non-exposed subjects with no history of primary or secondary renal diseases. Significantly higher urinary excretions of albumin and AMG were found in the workers exposed to silica. Silicotic subjects (n = 7) also had significantly high excretions of albumin, AMG, and NAG. All but one of the silicotic patients had ceased exposure from three to 17 years before the study. Our findings suggest that prolonged exposure to silica is associated with chronic irreversible nephrotoxicity in exposed workers.