The Snow Mountain Agent (SMA) is a Norwalk-like viral agent of acute gastroenteritis that has been detected only by immune electron microscopy (IEM). We established a solid phase microtiter radioimmunoassay (RIA) for SMA antigen employing pre-and post-challenge sera from volunteer studies as capture antibodies. SMA was detected in 12 of 67 stool samples from volunteers who were ill after oral challenge with SMA. All samples in which virus particles were detected by IEM were positive by RIA, but the RIA was 10-80 times more sensitive than IEM. To detect serum antibody to SMA, a blocking test was developed, employing diarrheal stool containing SMA as a standard source of antigen. Serum antibody rises were detected in eight out of nine volunteers with experimentally induced illness following challenge with SMA, as well as in three out of three naturally occurring cases. A preliminary sero-epidemiologic survey suggested that infection with SMA was common in the population surveyed. This RIA should permit large scale seroepidemiologic studies of SMA to be carried out, and should also facilitate characterization of this agent.