Abstract To determine whether developmental nicotine exposure (DNE) alters the ventilatory and metabolic response to hyperthermia in neonatal rats (postnatal age 2–4 days), pregnant dams were exposed to nicotine (6 mg kg−1 of nicotine tartrate daily) or saline with an osmotic mini‐pump implanted subdermally on the 5th day of gestation. Rat pups (a total of 72 controls and 72 DNE pups) were studied under thermoneutral conditions (chamber temperature 33°C) and during moderate thermal stress (37.5°C). In all pups, core temperature was similar to chamber temperature, with no treatment effects. The rates of pulmonary ventilation (VI), O2 consumption (VO2) and CO2 production (VCO2) did not change with hyperthermia in either control or DNE pups. However, VI was lower in DNE pups at both chamber temperatures, while the duration of spontaneous apnoeas was longer in DNE pups than in controls at 33°C. The VI/ VO2 ratio increased at 37.5°C in control pups, but did not change in DNE pups. To simulate severe thermal stress, additional pups were studied at 33°C and 43°C. VI increased with heating in control pups, but not DNE pups. As heat stress continued, gasping was evoked in both groups, with no effect of DNE on the gasping pattern. Over a 20‐minute recovery period at 33°C, VI returned to baseline in control pups, but remained depressed in DNE pups. In addition to altering baseline VI and apnoea duration, DNE is associated with subtle but significant alterations in the ventilatory response to hyperthermia in neonatal rats. This article is protected by copyright. All rights reserved