Exposure of HeLa S3 cells to high hydrostatic pressure (6.89 x 10(3) to 6.89 x 10(4) kPa: 1000 to 10,000 lbfin-2) reduced core and H1 histone mRNA levels as determined by hybridization to specific histone DNA probes. At 4.14 x 10(4) kPa for 10 min core histone and H1 histone mRNA levels were reduced 32-38% and 56%, respectively. At 30 min postdecompression core mRNA levels returned to atmospheric control levels while H1 histone mRNA levels continued to be suppressed. Levels of macromolecular synthesis were monitored under hydrostatic pressure with radioactive precursors of RNA, DNA and protein. Macromolecular synthesis was shown to be suppressed in a dose-dependent manner with increasing magnitude and duration of pressure. To determine the influence of pressure on histone mRNA stability, actinomycin D (10 micrograms ml-1) was used to block RNA synthesis. Relative amounts of H4 and H1 mRNA were determined at atmospheric pressure and following treatment with actinomycin D (10 micrograms ml-1), pressure (4.14 x 10(4) kPa) and a combination of pressure and actinomycin D. This study shows that a synthesis component and a stability component are involved in the pressure-induced reduction of core histone mRNA. At 4.14 x 10(4) kPa for 15 min, there was a 42% reduction in core histone mRNA of which approximately one third was due a suppression of transcription and two thirds to a loss of mRNA stability. The pressure-induced reduction in histone mRNA is attributed to the instability of endogenous histone mRNA and a reduction in transcription/processing of new histone mRNA.