Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for trends, using original cancer registry diagnoses. Results indicate a significant increase in incidence during 1973-80 for pleural mesothelioma among white males older than 55 at time of diagnosis but not for other age-race-sex-site subgroups. A histopathologic review of New York State and Los Angeles County cases by two independent pathologists, expert in the diagnosis of mesothelioma, lowered the overall estimates but a significant upward trend remained. The observed trend does not appear to be related to changes in diagnostic practice. The results of a five-member panel of expert pathologists will be published in a separate methodology paper.