Strains of adenovirus types 19 (Ad-19) and 37 (Ad-37) isolated from cases of epidemic keratoconjunctivitis (EKC) over a 10-year period were analyzed for differences in antigenic and restriction enzyme patterns. By restriction analysis, 35% of the isolates recovered between 1973 and 1981 and typed by hemagglutination-inhibition tests as Ad-19 were in fact Ad-37. This finding was confirmed by comprehensive serologic tests when Ad-37 reagents became available in 1981. All Ad-19 strains isolated between 1973 and 1980 were identical to the previously described genotype Ad-19A, and these Ad-19A strains exhibited a differential hemagglutination profile distinct from that of Ad-19 and Ad-37 prototypes. The earliest Ad-37 case found in the United States occurred in April 1976; Ad-37 then became the major agent of EKC from 1977 to 1983. Intermediate strains between types 19A and 37 were not detected by either antigenic or restriction fragment analyses. Thus, some genetic event appears to generate new genotypes such as Ad-19A and serotypes such as Ad-37.