Two Epstein-Barr nuclear antigen-negative cell lines, EW36 and CA46, derived from human undifferentiated lymphomas were exposed to the methylxanthines theophylline and 3-isobutyl-1-methylxanthine. Both compounds markedly increased the proportion of cells which bears complement receptors, whereas other surface markers such as surface immunoglobulin and IgG Fc receptors were unchanged. The inducing agents, hexamethylene bisacetamide and diethylsulfoxide, had a similar effect, but other compounds known to alter intracellular cyclic AMP had no effect on surface markers. The expression of complement receptors first appeared at 8 to 10 hours and was dependent upon the continued presence of theophylline in the tissue culture medium. Other effects of the methylxanthine derivatives tested included inhibition of DNA synthesis and a reduction in mean cellular volume. However, inhibition of growth per se did not result in complement receptor induction. These data suggest that the differentiation agents active in this system may be useful tools in the study of human lymphoid malignancies.