Guinea-pigs were infected subcutaneously or by respiratory challenge with plasmid-containing (pPst+pCad+pFra+) Yersinia pestis strain 358 and its pPst-pCad+pFra+, pPst+pCad+pFra- and pPst-pCad+pFra- derivatives, grown in vitro at 28 degrees C or at 37 degrees C. Lack of plasmid pPst did not lead to an increase in LD50 with either route of challenge. When the virulence of the four Y. pestis strains grown at the two temperatures was compared, the LD50 values of those grown at 37 degrees C were lower. Respiratory challenge with cultures grown at 37 degrees C mimics the man-to-man pneumonic plague cycle. The average LD50 values decreased c. two-fold and 10-fold for pPst+ and pPst- Y. pestis variants, respectively. The data suggest that historical epidemic outbreaks of pneumonic plague in the human population residing in the Caucasus region where there are natural plague foci in common voles may have been caused by pPst- Y. pestis strains.