A radioimmunoassay (RIA) for DSIP-like material was established in unextracted human plasma. Most of the immunoreactivity was found in a "large" fraction while a much smaller amount co-eluted with DSIP from Sephadex as a "free" fraction. Both peaks progressively increased with increasing amounts of added DSIP. Acidification, but not treatment with charcoal-dextran, resulted in a relative decrease in the "large" peak and an increase in the "free" peak. This RIA, therefore, appears to measure both bound and free forms of DSIP-like immunoreactivity, the levels of which were higher at 4 p.m. than at 8 a.m.