Eleven outbreaks of acute gastroenteritis, eight of which were in nursing homes or retirement facilities, were reported in virginia during the winter of 1993-1994. Serum samples (four outbreaks) and stool samples (two outbreaks) from involved people were tested for human calicivirus (HuCV) infection by enzyme immune assays (EIAs) using recombinant Norwalk virus (rNV) and Mexico virus (rMX) capsid antigens and reverse transcription-polymerase chain reaction (RT-PCR). Of the 31 pairs of acute and convalescent serum specimens tested, 24 had a fourfold or more titer increase to rMX and 4 responded to rNV. In all four outbreaks, the geometric mean titers (GMTs) against rMX were significantly higher than those against rNV in the convalescent, but not in the acute phase of illness. The antibody response to rMX among these patients was also higher than to rNV (summary mean 32-fold increase vs. 0.7-fold increase, respectively, P < .001). Antigen was detected in 5 of 21 stool specimens tested by the rMX EIA, RNA in 12 of 17 stool specimens tested by RT-PCR, and small round structured virus (SRSV) particles in 12 of 21 by electron microscopy (EM); none were positive by the rNV EIA. Sequence analysis of the RT-PCR-amplified products from the viral RNA polymerase region revealed 92-93% amino acid identity with Snow Mountain agent (SMA), 86% with MX, 58-59% with NV, and 31-32% with Sapporo HuCV, suggesting that these viruses belong to the SMA HuCV genogroup.