Using a modified immunoblot procedure we looked for early serological markers of disease progression in sequential serum samples from 30 initially symptomless HIV-infected homosexual men. Sixteen men who did not progress beyond persistent generalized lymphadenopathy (PGL) and did not develop HIV antigenaemia showed persistent strong immunoglobulin G (IgG) reactivity to all initially recognized HIV proteins. Three out of four men who did not progress beyond PGL but did develop HIV antigenaemia showed declining or absent IgG reactivity to the outer HIV core protein p17, whereas reactivity to other initially recognized HIV proteins persisted in all four; in one of these subjects a striking decline in anti-p17 reactivity occurred 1 1/2 months after HIV antibody seroconversion and 7 1/2 months before HIV antigenaemia developed. In nine out of 10 men who developed constitutional disease [Centers for Disease Control (CDC) group IV A] or AIDS (CDC groups IV C1 and IV D), a decline in anti-p17 reactivity was seen preceding or at disease development; in two of these men a concomitant decline in anti-p24 reactivity was seen. In the only individual without HIV antigenaemia who developed CDC group IV disease, anti-p17 reactivity declined 10 months before disease development, whereas no similar decline in anti-p24 reactivity was seen. Decline in IgG antibody reactivity to HIV core protein p17 appears to be an earlier marker of disease progression than the previously reported decline in anti-p24 reactivity, and may be of value in selecting individuals for secondary prevention of HIV-related disease development.