This study examined the ability of atria from neonatal and middle-aged noninsulin-dependent diabetic rat models to respond to both adenosine and isoprenaline. 2. Cumulative additions of adenosine (1-1000 microM) produced concentration-dependent decreases in the force of contraction of rat atria that were unchanged in neonatal diabetic animals. Although direct inotropic responses to adenosine were unchanged, atria from neonatal diabetic animals exhibited an increase in maximum response to adenosine-induced antiadrenergic effect. 3. Atria from middle-aged noninsulin-dependent diabetic rats exhibited a supersensitivity to the direct inotropic effect of adenosine compared with atria from age-matched control rats. The middle-aged, noninsulin-dependent diabetic state did not alter the maximum response of atria to adenosine-induced antiadrenergic effect. 4. A comparison was made between middle-aged (10-month-old) controls and young (4-month-old) controls. Atria from middle-aged control animals exhibited a lower sensitivity and responsiveness to the direct inotropic effect of adenosine compared with those from young controls. 5. Cumulative additions of isoprenaline (10(-9)-10(-6) M) produced concentration-dependent increases in inotropy that were unchanged in atria from either neonatal or middle-aged noninsulin-dependent diabetic rats. 6. These results show that neonatal and middle-aged noninsulin-dependent diabetes and age-related factors lead to significant changes in atrial reactivity to the adenosine-induced stimulation in the absence and presence of isoprenaline. However; isoprenaline-induced positive inotropic response cannot change in each diabetic heart to an apparent extent.