The involvement of immunological reactivity to ranitidine base (R-b) and ranitidine hydrochloride (R-HCl) in the development of occupationally related symptomatology was analyzed in 40 subjects employed in a pharmaceutical plant producing ranitidine and in 33 nonexposed controls, using a specific dose-response lymphocyte proliferative test (lymphocyte transformation test: LTT). Of the 40 workers, 11 (28%) gave positive reactions to LTT: 3/11 to R-b, 4/11 to R-HCl, and 4/11 to both compounds. None of the controls gave positive reactions. Cutaneous, oculonasal, or respiratory work-related symptoms were cited by 23 of the 40 (58%) subjects; ten of these 23 subjects (43%) were LTT positive. One asymptomatic case was LTT positive. The present results indicate that specific immune reactivity to ranitidine, analyzed by LTT, is associated with the presence of occupational symptomatology; R-HCl and R-b seem to share some antigenic determinants, because of the partial cross-reactivity shown by the examined compounds. Nonimmunological, probably irritative, mechanisms are also present in some of the symptomatic subjects.