Reconstruction experiments have shown that temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1)(Glasgow strain 17) grow, complement, and recombine with similar efficiency in human nerve ganglion cells, human brain cells, normal human fibroblasts (WI38), and baby hamster kidney (BHK) 21/C13 hamster cells. Cultures of human trigeminal, superior cervical, and vagus ganglia that had failed to release herpes simplex virus spontaneously were superinfected with a range of ts mutants of HSV-1 and incubated at both permissive (31 degrees C) and nonpermissive (38.5 degrees C) temperatures. Progeny virus was assayed at both temperatures to determine if complementation of or recombination with the input genomes had occurred. The results showed that the ganglia from 8 of 14 individuals, which had been consistently negative for spontaneous release of virus, contained information that could be detected or rescued following superinfection with ts mutants of herpes simplex virus. In two additional cases, positive results were obtained after the superinfection of negative ganglia explants, but in each of these herpes simplex virus had previously been spontaneously released from one of six ganglia explanted.