Protein synthesis in cancerous and normal human endometrium was investigated by the incorporation of [35S]methionine and analysis of products by two-dimensional polyacrylamide gel electrophoresis. Comparison of the cellular products from organ cultures of endometrial carcinoma, obtained from each subject before and after in vivo administration of medroxyprogesterone acetate (MPA) for 10-14 days revealed: (i) a decrease in the synthesis of tubulin and of a protein of molecular weight (mol. wt) 68 kDa, isoelectric point (pI) 6.0, and (ii) an increase in the synthesis of creatine kinase (CK) and of protein of mol. wt 36 kDa, pI 4, following MPA therapy. The 68 kDa protein was expressed at relatively reduced levels in organ cultures of normal human endometrium throughout the menstrual cycle. In primary cultures of normal human endometrium throughout the menstrual cycle. In primary cultures from cancerous endometrium endometrium established for several weeks the 68 kDa protein was not expressed but could be induced by heatshock. Primary cultures were also used to investigate the early events following progesterone stimulation which revealed a decrease in synthesis of a protein mol. wt 36 kDa, pI 8 at 8 h following administration.