Human beta-interferon (IFN) induced an antiviral state in two fetal brain and six glioma cell lines. The growth-inhibitory effect of IFN was most pronounced on three glioblastoma lines and least on fetal brain and oligodendroglioma cells; IFN growth inhibition of one schwannoma and one anaplastic cell line was intermediate between the two other groups. Thus, the growth-inhibitory effect of IFN generally correlated with the degree of anaplasia of the tissue from which the cells were derived. IFN (1000 units/ml) had to be present for 24 to 48 hr to have a significant inhibitory effect on growth of glioblastoma (12-18) cells. However, growth inhibition of 12-18 cells exposed to IFN for 3 days persisted for 3 weeks. Both sialic acid-N-acetylgalactosamine ganglioside and a mixture of normal human brain gangliosides (50 microM) inhibited growth of fetal brain (CHII) but not glioblastoma 12-18 cells. However, preincubation of cells with either sialic acid-N-acetylgalactosamine or a mixture of gangliosides did not augment the growth-inhibitory effects of IFN on either CHII or 12-18. These results indicate that gangliosides and IFN may be operating through different mechanisms to cause growth inhibition.