The development and persistence of Sendai virus-specific CD4(+) T cell memory has been analyzed following respiratory infection of C57BL/6J mice by determining the prevalence of IL-2-producing Th cell precursors (Thp), Frequencies as high as 1:40 virus-specific CD4(+) T cells were found in the regional lymph nodes and spleen during the acute phase of the host response and persisted at levels greater than or equal to 1:500 for 2 to 3 mo, Thereafter, these CD4(+) T cells tended to distribute more to the spleen than to the lymph nodes, a pattern that persisted for the life of the animals, From 3 to 12 mo after infection, virus-specific Thp were always detectable, although the numbers mere diminished relative to those measured during the acute phase, Thereafter, however, in both contemporary and cumulative assays, there was a progressive increase in both the frequency and number of Thp, These increases were especially apparent for mice more than 2 years of age, This may reflect enrichment of the CD4(+)CD44(high) memory set due to the gradual diminution of the naive CD4(+)CD62L(high)CD44(low) component. Analysis of DNA staining profiles for the CD4(+) T cells showed high levels of cycling for the acute phase of the response, whereas the rate of T cell turnover measured for the CD4(+)CD44(high) population by bromodeoxyuridine incorporation indicated a pattern of stable, continuing proliferation throughout Life, Virus-specific CD4(+) T cell memory resulting from a single exposure to a readily eliminated RNA virus is thus maintained indefinitely in laboratory mice.