The methacholine inhalation challenge test (MIC) was used to evaluate bronchial responsiveness in 67 children who were the products of multiple pregnancies when they were 7-15 years old. At birth, 30 (45%) infants had intrauterine growth retardation (IUGR; birth weight <2 SD below normal birth weight, or birth weight difference >1.3 SD between twin-pairs), and 59 (88%) were born before 37 weeks of gestation. None of the children had doctor-diagnosed asthma. The provocative dose of methacholine causing a 20% fall in Wright's peak expiratory flow (WPEF) (PD20) was below 1,000 microg in 10 (15%) children, and they were classified as MIC responders. There were no differences in perinatal or neonatal factors between MIC responders and nonresponders; in particular, MIC responses did not differ between IUGR infants, and children with appropriate growth for gestational age (AGA) at birth. There were seven discordant pairs in which one child was a MIC responder and the other was not; 5 responders were IUGR, and 2 were AGA children (ns). Respiratory tract infections after the neonatal period were equally common in IUGR and AGA children. However, these infections were associated with later bronchial hyperresponsiveness. Doctor-diagnosed respiratory infections, numbers of antibiotic courses, episodes of otitis media, and the need for adenoidectomy, tonsillectomy, and tympanostomy were more common in MIC responders than in nonresponders. We conclude that IUGR was not associated with subsequent bronchial hyperresponsiveness in twin pairs assessed by the MIC test. A significant relationship was seen between bronchial hyperresponsiveness and infections after the neonatal period.