The in vitro swelling of human sperm nuclei in the presence of sodium dodecyl sulphate (SDS) was studied by counting swollen sperm nuclei in a microscopic preparation and by measuring the decrease of optical density at 600 nm (OD600). At pH 8.0 or lower, OD600 showed a linear relationship to the sperm count. At higher pH values a fraction of the nuclei became swollen and OD600 decreased proportionally, although the sperm count did not change in the first 2 hr. The fraction of swollen sperm nuclei increased with time and by raising the pH or temperature. The swelling occurred only in the presence of SDS and was the consequence of a binding of SDS to the hydrophobic regions of the nuclear proteins.