To determine effects of aging and autonomic input on interrelationships between respiratory and heart rate variability, we collected 5 min of lung volume of R-R interval data from 7 young [27 +/- 3(SD) yr] and 10 older (69 +/- 6 yr) healthy supine humans before and after double pharmacological autonomic blockade with propranolol (0.2 mg/kg iv) and atropine (0.04 mg/kg iv). Estimates of respiratory and heart rate power spectra and linear transfer functions between the two groups were generated by Fourier analysis. Age, double blockade effects, the age-drug interactions were determined by analysis of variance for repeated measures. Basal R-R intervals were unaffected by age. Double blockade decreased R-R intervals and variability in both age groups (P < 0.0001), but R-R intervals decreased less in older than in young subjects (P < 0.0001). In contrast, basal respiratory intervals and standard deviation were greater in older subjects (P = 0.05) and were unaffected by double blockade in young and older subjects. Lung volume-to-heart rate spectral coherence was highest at frequencies associated with respiration and greater in young than in older subjects (P < 0.07). Double blockade decreased lung volume-to-heart rate variability transfer function magnitude (P < 0.007) and increased phase angle (P < 0.02) without age effects or age-drug interactions. In conclusion, heart rate, respiration, and respiration-heart rate interrelations are altered by aging, and double autonomic pharmacological blockade does not eliminate all age-related differences.