The intravenous injection of hapten-modified (picrylated) cells causes unresponsiveness. When conventional or recombinant interleukin-2 (IL-2) is also injected, strong contact sensitivity occurs. This IL-2 is effective when given 7 hr after the injection of the picrylated cells or 2 days later, but has no effect when given beforehand. It is suggested that picrylated cells given intravenously fail to induce contact sensitivity secondary to a failure of IL-2 production, and that IL-2 may be one of the second signals which converts a 'tolerogenic' stimulus into an immunogenic stimulus.