The effects of four subtypes of recombinant human alpha interferon (RIFNα), (A, B, D, and the hybrid A/D) were tested on six strains of herpes simplex virus (HSV).RIFNα-D was the most effective subtype in rabbit kidney cells, which is consistent with our previousin vivoresults in the rabbit herpetic keratitis model. In human corneal cells, however, RIFNα-D was one of the least effective IFN subtypes tested. Conversely, RIFNα-A appeared to be relatively more effective in the human corneal cells than in the rabbit kidney cells, but RIFNα-B and RIFNα-A/D were the most effective interferon subtypes in human corneal cells. Different strains of HSV had different susceptibilities to the various IFN subtypes tested.