We examined the effect of animal strain, type of spasmogen, and mode of spasmogen administration on the pattern of lung mechanical responses in intubated and mechanically ventilated mice. We determined the response in inspiratory respiratory system resistance (R(rs)) and inspiratory static respiratory system compliance (C(rs)) to increasing doses of inhaled or intravenous carbachol or serotonin in Balb/C and C57BL/6 mice. R(rs) responsiveness was quantitated by calculating, by interpolation, the inhaled spasmogen concentration (PC(150)) and intravenous spasmogen dose (PD(150)) causing an increase in R(rs) to 150% of baseline. C(rs) responsiveness was calculated similarly for a decrease in C(rs) to 85% of baseline (PC(85) for inhaled and PD(85) for intravenous spasmogen). Baseline R(rs) and C(rs) were similar in all groups. R(rs) responsiveness to inhaled and intravenous carbachol and serotonin tended to plateau and was not different in the two strains. In contrast, C(rs) responses were variable and had a greater mean PC(85) for inhaled serotonin than carbachol in both strains and a greater fall in mean C(rs) at PC(150) for carbachol in Balb/C mice; no interstrain and interdrug differences in PD(85) were noted for intravenous spasmogens. Intravenous atropine attenuated the R(rs) response to high-dose inhaled and intravenous serotonin, suggesting the involvement of a vagal reflex. In contrast, atropine attenuated C(rs) responses only for intravenous serotonin in Balb/C mice. These results suggest that animal strain, spasmogen, and mode of administration determine the extent to which induced airflow resistance is accompanied by increases in elastic recoil.