Alterations in tissue viscance (Vti) and collateral resistance (Rcoll) are both used as indexes of peripheral lung responses. However, it is not known whether the two responses reflect the effects of activation of the same contractile elements. We measured differential responses in Vti and Rcoll to histamine and leukotriene (LT) C4 to determine whether each evoked a similar pattern of response. Using the wedged bronchoscope constant-flow technique, we measured Rcoll in lobar segments of anesthetized, paralyzed, open-chest, mechanically ventilated mongrel dogs. In addition, we measured (with an alveolar capsule) alveolar pressure (PA) within the segment under study. This allowed us to calculate Vti, the component of the PA change in phase with segment flow. Rcoll and Vti measurements were obtained under base-line conditions and after local delivery of aerosols generated from histamine and LTC4. In five out of five lobes studied with both histamine and LTC4, the fractional Rcoll response to histamine was greater than the fractional Rcoll response to LTC4. In contrast, in four out of five lobes examined, the fractional increase in Vti accompanying the histamine response was less than the fractional increase in Vti accompanying LTC4 administration. These data suggest that anatomically distinct contractile elements influence Vti and Rcoll insofar as LTC4 and histamine evoke quantitatively different changes in these two indexes of peripheral lung responses.