Acute/early HIV infection is a period of heightened HIV transmission and a window of opportunity for intervention to prevent onward disease transmission. The NIMH Multisite Acute HIV Infection (AHI) Study was an exploratory initiative aimed at determining the feasibility of recruiting persons with AHI into research, assessing their psychosocial and behavioral characteristics, and examining short-term changes in these characteristics. This paper reports on lessons learned in the study, including: (1) the need to establish the cost-effectiveness of AHI testing; (2) challenges to identifying persons with AHI; (3) the need to increase awareness of acute-phase HIV transmission risks; (4) determining the goals of behavioral interventions following AHI diagnosis; and (5) the need for "rapid response" public health systems that can move quickly enough to intervene while persons are still in the AHI stage. There are untapped opportunities for behavioral and medical science collaborations in these areas that could reduce the incidence of HIV infection.