The influence of delta 9-tetrahydrocannabinol (delta 9-THC) on the cellular levels of histone mRNAs and ribosomal RNAs was examined in several normal and transformed human cell lines--HeLa S3 cells, WI-38 human diploid fibroblasts, SV40-transformed WI-38 cells, and A549 lung carcinoma cells. RNA sequences were quantitatively assayed by electrophoretic fractionation, transfer to nitrocellulose, and hybridization with cloned genomic human histone or ribosomal DNA sequences. Treatment with delta 9-THC (10-40 microM) for 10 hr resulted in a concentration-dependent decrease in the representation of H2A, H2B, H3 and H4 histone mRNAs without a significant inhibitory effect on the levels of ribosomal RNAs. The cannabinoid-mediated inhibitory effect on histone gene expression was less evident in cells with active drug-metabolizing systems.