Organophosphate-based pesticides have been associated with pathology and chromosomal damage in humans. There are also epidemiologic links with cancer. The few screening tests for low-level occupational exposure are of doubtful sensitivity; this investigation evaluated four methods. Blood samples were studied from 10 farmers before and after occupational exposure to organophosphate-based pesticides and five unexposed controls. The standard cholinesterase test was insensitive to the exposure (P=0.815). However, a significant increase in Howell-Jolly bodies within erythrocytes was observed (P=0.001). Cytogenetic studies on routine and aphidicolin-induced blood cultures revealed that following organophosphate exposure the total number of gaps and breaks on human chromosomes was significantly increased (P=0.004 and P=0.0006, respectively). We concluded that Howell-Jolly body and fragile site analysis were sensitive indicators of nuclear damage resulting from low-level occupational exposure to organophosphate. Such nuclear damage could be implicated in carcinogenesis. The development of bladder cancer is one such example.