We report the temporal association of interferon (IFN) and p27 core antigen production during experimental simian immunodeficiency virus Delta B670 (SIV) infection in rhesus monkeys. Peak serum IFN-alpha levels (10(2.8-5.0)U/ml) occurred 10 days post infection (p.i.) and peak p27 levels (3.1-34.4 ng/ml) occurred 10-14 days p.i. Acid-stable IFN-alpha (10(1.6-2.5)U/ml) was detected 3-5 days before p27 in sera from three monkeys and was detected with p27 (0.06-3.06 ng/ml) in four monkeys during the primary infection. Serum IFN-alpha and p27 levels became undetectable 24-40 days p.i. Two monkeys remained asymptomatic for SIV after the primary p27 antigenaemia, three monkeys had recrudescent (3-4 months p.i.) acid stable interferonaemias (10(1-2.5)U/ml) with p27 antigenaemias (0.06-2.7 ng/ml) that persisted until death, and two monkeys had acute SIV infections (died < or = 7 months p.i.) with persistent acid-stable interferonaemia (10(1.6-2.5)U/ml) and p27 antigenaemia (6-9 ng/ml). Our results indicate that the detection of acid-stable IFN-alpha in serum is closely associated with detection of p27 (P = 0.0001) and suggest that detection of acid-stable IFN-alpha and p27 core antigen is indicative of active SIV infection.