The expression of the recently described rap genes, closely related in the effector region to the ras proto-oncogenes, was examined by Northern blot analysis in 41 primary human tumors. The structural and in vitro biological properties of the rap gene products suggest their possible antagonistic action in the same effector pathway as the ras proteins. In order to determine whether a deregulation in the rap transcription levels could be involved per se in the multistep carcinogenic process, we chose to analyze tumors for which the ras mutation rate was previously reported to be extremely rare or unknown, i.e., non-Hodgkin's lymphomas, certain types of carcinoma, sarcomas, germinal neoplasms of the testes and various tumors of the nervous system. A severe decrease in the expression of the rap1A gene was shown in the fibrosarcomas and the adenocarcinoma of the salivary gland studied, as compared to their normal counterparts, whereas no rap2 expression was found in the polyadenylated RNA of sarcoma samples.