Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB.