The response of peripheral blood lymphocytes to the streptococcal preparation OK432 was examined in vitro in 193 gastric cancer patients. When the patients were divided by stimulation index (SI) into two groups, SI > or = 20 and SI < 20, the response rate of SI > or = 20 group of stage IV was 37.5%, and higher than those of the other stages (p < 0.05). In the relationship between SI and the survival period in stage III, the SI > or = 20 group showed longer survival than the SI < 20 group (p < 0.05). There was no statistically significant difference in survival between SI > or = 20 and SI < 20 in stage IV, but no member of the SI < 20 group survived more than 2 years, whereas the five-year survival of the SI > or = 20 group was 38.9%. In the overall survival of stage III and IV, the SI > or = 20 group showed longer survival than the SI < 20 group (p = 0.001). The lymphoproliferative responses to OK432 decreased in very advanced gastric cancer patients and this might lead to poor prognosis.