To evaluate the kinetics of functional effector and memory T help in vivo the effect of priming with one serotype of vesicular stomatitis virus-Indiana (VSV-IND) on the antibody response to a serologically distinct heterologous second serotype (VSV-New Jersey: VSV-NJ) was studied. Mice primed with VSV-IND 4 or 8 days before being given a second infection of VSV-NJ developed an earlier and enhanced IgG response to neutralizing determinants of the second VSV serotype. However, this enhanced response was not detected in mice primed 15 or more days prior to a second infection. After 15 days, mice challenged with the heterologous VSV-NJ mounted a strictly normal primary response without evidence of suppression. It was shown by in vivo time-kinetics experiments that efficient VSV cross-reactive T help, capable of enhancing the IgG response is short lived and cyclosporin A resistant. Adoptive transfer experiments demonstrated in the absence of experimental evidence for suppression that this short-lived capacity to enhance neutralizing IgG antibody responses is mediated by T cells. These findings have implications for understanding antiviral protection and immunological memory against related but serologically distinct viruses.