To examine whether and at what stage mucosal immune responsiveness is impaired during HIV-1 infection. Intestinal and systemic antibody-secreting cell (ASC) responses were examined in eight HIV-1-infected volunteers and 10 seronegative control subjects after oral cholera and parenteral tetanus vaccinations. ASC numbers were determined before and after booster vaccinations by the enzyme-linked immunospot (ELISPOT) technique. This technique was performed on cell suspensions obtained from enzymatically dispersed duodenal biopsies and from peripheral blood. Oral cholera vaccination evoked ASC responses in the intestinal mucosa of six out of eight HIV-1-infected volunteers, including patients with advanced disease and very low levels of circulating CD4+ T cells. The intestinal cholera ASC responses in HIV-infected volunteers were comparable to those in uninfected controls with regard to both magnitude and distribution of antibody classes. Most HIV-infected volunteers with only moderately reduced CD4+ T-cell counts also responded with vaccine-specific ASC in the blood, whereas none of the patients with < 200 x 10(6)/l CD4+ T cells per litre blood had detectable circulating ASC. These findings indicate that mucosal humoral immune responsiveness to a T-cell dependent antigen is maintained in HIV-infected individuals, despite concomitant systemic humoral hyporesponsiveness.