We analyzed data from a prospective cohort study of injection drug users (IDUs) attending methadone treatment clinics in Bangkok, Thailand, during 1995-1998 to characterize factors associated with a period of high incidence (PHI) from July 1996 through January 1997 compared with periods of lower incidence. Sociobehavioral characteristics were similar for all participants during and outside the PHI except for the following: there was more reported drug injection while IDUs were incarcerated during the PHI (odds ratio, 1.67; p =.02) and significantly higher proportions of persons reported heroin injection (91% vs. 75%, respectively; p =.02) and higher frequencies of daily injection and sharing of injection equipment (40% vs. 25%, respectively; p =.05) during the PHI than outside the PHI. Through most of the first year after seroconversion, plasma HIV-1 loads were significantly higher in persons who seroconverted during the PHI than in those who seroconverted outside the PHI. Higher viral loads may potentially contribute to faster disease progression and increased infectiousness or transmissibility to subsequent contacts. Our findings suggest that prevention efforts to reduce the effective size and turnover within IDU sharing networks may have a significant impact on the epidemic by disrupting the rapid transmission of HIV-1 from recently infected, highly infectious individuals.