Research needs to build evidence for the roles that HIV status of injection partners may or may not play in injection risk behaviors of injection drug users (IDUs). Using baseline data collected from a randomized controlled study (INSPIRE) conducted in four cities (Baltimore, Miami, New York, and San Francisco) from 2001 to 2005, we categorized 759 primarily heterosexual HIV-positive IDUs into four groups based on HIV serostatus of drug injection partners. Thirty-two percent of the sample injected exclusively with HIV-positive partners in the past 3 months and more than 60% had risky injection behavior with these partners. Eight percent injected exclusively with HIV-negative partners and 49% injected with any unknown status partners. The remaining 11% reported having both HIV-positive and -negative injection partners, but no partners of unknown HIV status. Riskier injection behavior was found among the group with mixed status partners. The risk among the group with any unknown status partners appeared to be driven by the greater number of injection partners. No major group differences were observed in socio-demographic and psychosocial factors. Our analysis suggests that serosorting appeared to be occurring among some, but not an overwhelming majority of HIV-positive IDUs, and knowledge of HIV status of all injection partners per se did not appear to be as important as knowledge of sexual partner's HIV status in its association with risk behavior.