We completed a nested case-control analysis of factors associated with reporting a high pesticide exposure event (HPEE) by pesticide applicators and spouses during the five years since enrollment in the Agricultural Health Study (AHS). Cases and controls were identified from the 16,415 private pesticide applicators and 14,045 spouses with completed five-year follow-up interviews as of October 2000. Among the applicators, 306 cases with at least one HPEE in the five years since enrollment and 612 controls, randomly selected from those without a reported HPEE, were identified for analysis. Among the spouses, 63 cases were identified and 126 controls were selected. Risk for a new HPEE was increased among applicators reporting at enrollment ever having an HPEE with an odds ratio (OR) of 3.8 (95% CI: 2.7, 5.3). Compared to applicators who applied pesticides fewer than 5 days per year, the ORs ranged from 1.4 (95% CI: 0.9, 2.2) for 6 to 10 days per year to 2.2 (95% CI: 1.4, 3.6) for more than 20 application days per year. The incidence of HPEE among Iowa applicators was much greater (8.8/1000 applicators) than among North Carolina applicators (2.0/1000). Spouses reported fewer HPEEs compared to applicators (2/1000 spouses). Overall, the observed risk factors for new HPEEs among applicators are similar to risk factors observed in previous cross-sectional analyses of HPEE history. Further, only 13% of applicators and 22% of spouses with symptoms resulting from HPEE sought medical care, suggesting that pesticide poisoning surveillance data may seriously underreport the frequency of such events.