The capacity of interferon (IFN) to induce the enzyme 2',5'-oligoadenylate synthetase (2',5'-A synthetase) in malignant cells from freshly explanted solid tumors was investigated. The malignant cells were separated from non-malignant cells by using velocity and density gradient sedimentation as well as adherence on plastic. During the test the cells were usually maintained on an extracellular matrix (ECM) in the wells of a microplate for 24 h. The tumor cells varied in their sensitivity to IFN-induced enhancement of 2',5'-A synthetase. In five out of 28 tumor samples natural alpha-IFN induced no major enhancement in the intracellular levels of 2',5'-A synthetase. The effect was dose-dependent and as little as 0.5 units of alpha-IFN/ml was sufficient to cause an increase in the intracellular levels of this enzyme. Some tumors differed in their susceptibility to alpha-, beta- and gamma-IFN, showing resistance to one IFN-type and sensitivity to the other two. As little as 6 X 10(3) cells/well were required for measuring the induction of 2',5'-A synthetase. Measurement of induction of 2',5'-A synthetase by IFN in vitro could have clinical relevance for pre-treatment testing of the susceptibility of primary tumor cells to IFN.