Syncytium formation, a feature of HIV-1-induced cytopathology, allows the virus to propagate through cell-to-cell spread. An assay has been developed to measure antibodies (syncytium inhibition, SI) that inhibit this process. Two cell lines were used: the indicator cells, which are not HIV-1 infected, bear CD4 receptors on their surface; the fusogenic HIV-1 infected cells, which do not release virus but are responsible for initiating syncytium formation, are free of CD4 receptors. Co-cultivation of about 10(5) of each of these cells induces the emergence of 70-100 multinucleated giant cells within 48 h. Sera from 34 children born to HIV-1-infected mothers were tested by western blot (WB) and SI assay. SI antibodies were detected in the blood of 15 (65%) of 23 WB-positive children and in none of 11 WB-negative children. There were striking differences in prevalence and titre of SI antibodies in children with lymphocytic interstitial pneumonitis (LIP) compared with those with opportunistic infections (OI). All 8 children with LIP had SI antibodies ranging in titre from 40 to greater than 320. By contrast, only 2 of 7 with OI had SI antibodies, in both of whom the SI titre was 20 (p less than 0.05). No sera from children who had seroreverted contained SI antibodies. The findings point to the need to identify the specific HIV-I peptides or epitopes responsible for syncytium formation since SI antibodies correlate with clinical outcome in children.