ISEE-250 Introduction: Metolachlor, a chloroacetanilide herbicide, is used for general weed control in many agricultural food and feed crops and in residential applications. One of the two most widely used herbicides in the U.S., metolachlor has been classified by the EPA as a “possible human carcinogen,” based on increased liver tumours in female rats. Studies in humans, however, are few, despite the considerable potential for occupational exposure and environmental exposure via drinking water. Investigations in the Agricultural Health Study (AHS) have shown an increased risk for haematopoetic cancers with increasing lifetime days exposure to another chloroacetanilide herbicide, alachlor, and an increased risk for lung cancer with metolachlor exposure. Aim: These results motivated further investigation of the cancer risk among applicators in the AHS who used metolachlor. Methods: We obtained detailed pesticide exposure information from 57,311 licensed pesticide applicators in Iowa and North Carolina, using a self-administered questionnaire completed at the time of enrolment (1993–1997). Cancer incidence was followed through December 31, 2001. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) for several types of cancer among metolachlor-exposed applicators, while adjusting for many potential confounders. Two exposure metrics were used: tertiles of lifetime days of exposure (LD) and tertiles of intensity-weighted lifetime days of exposure (IWLD). The IWLD metric incorporates a measure of potential exposure intensity based on application and methods, repair of application equipment and use of personal protective equipment. Results: 23,396 (41%) of the AHS applicators reported ever using metolachlor. Exposure was not associated with overall cancer incidence. Applicators in the highest tertile of LD had a significantly elevated risk for lung cancer (RR=2.5; 95%CI, 1.2–5.4, p-trend =0.01) and bladder cancer (RR=3.19; 95%CI, 1.05–9.74, p-trend=0.02), a non-significantly elevated risk for rectum cancer (RR=3.6; 95%CI, 0.9–14.7, p-trend =0.05), and a significantly decreased risk for prostate cancer (RR=0.7; 95%CI, 0.5–0.9, p-trend =0.04), compared with those in the lowest tertile. Results were similar for the IWLD metric, but non-significant. When we compared tertiles of exposure among metolachlor-exposed applicators to those who never applied metolachlor, results were null. No other cancer appeared to be associated with use of metolachlor. Discussion: There was an increased risk for lung cancer and a decreased risk for prostate cancer, with increasing LD exposure among metolachlor exposed applicators, however, there were inconsistencies between the two exposure metrics and with the comparison to applicators not exposed to metolachlor. There was a suggested increased risk for rectum cancer with increasing LD exposure, however, this estimate was based on 17 cases and should be interpreted with caution. Taking into consideration both exposure metrics, our analyses did not find any clear associations between metolachlor and these cancers.