Using mathematical modeling of respiratory rhythm generation and the breakpoint of breath holding, the dependence of gas-exchange dynamics and the duration of voluntary breath holding on chemoreceptor regulation of the respiratory system was studied. With data from experiments on ten volunteers who had performed their maximum breath holding after maximum inspiration and after maximum expiration, it was shown that experimentally obtained values of the duration of breath holding after expiration were approximately 70% of those predicted by the model. This is an estimation of the contribution of chemoreceptor control to breath holding. The results support the concept of the key role of chemoreceptors at the breakpoint of breath holding.