Excretion of herpes simplex virus (HSV) in the oral cavity was studied in eight human subjects with a history of herpes labialis. Serial intraoral specimens were obtained by gargling broth and examined for virus by centrifugal inoculation of primary human amnion cells. Forty-seven of 637 specimens (7.4%) contained HSV. The majority of isolates (62%) were found in clusters, and the rate of excretion was significantly increased during the common cold (21%) and after oral trauma (17%) (P = 0.001 and 0.04, respectively). Oral HSV excretion often occurred in parallel with episodes of herpes labialis but could not be attributed to viral contamination from a labial lesion. Each patient excreted only one strain of HSV type 1 as determined by restriction endonuclease analysis with KpnI and BamHI. Unexpectedly, prodromal symptoms of herpes labialis were commonly not followed by development of a lesion (false prodrome). False prodromes were associated with a high rate of oral HSV excretion (60%). Intraoral ulcers on the gingivae and hard palate were frequently associated with oral HSV excretion (31%) and are the most likely source of HSV in the oral cavity.