We studied the effects of two methods of synchronized mechanical ventilation [synchronized intermittent mandatory ventilation (SIMV) and assist/control (A/C)] on ventilation, gas exchange, patient effort, and arterial blood pressure (ABP) fluctuations. SIMV and A/C were applied in random order in 12 preterm neonates (gestational age, 29.7 +/- 2.3 weeks; birth weight, 1,217 +/- 402 g). We measured total (Vetot) and mechanical (Vemech) minute ventilation, spontaneous (Vtspont) and ventilator supported (Vtmech) tidal volume, transcutaneous oxygen saturation (SpO2), transcutaneous PO2 (TcPO2), and PCO2, (TcPCO2), mean airway pressure (Paw), phasic esophageal pressure deflections (Pe) as an estimate of inspiratory effort, mean arterial blood pressure (ABP), and beat-to-beat ABP fluctuations. The measurements obtained during conventional intermittent mandatory ventilation (IMV) were compared with the recordings during SIMV and A/C. To make the measurement conditions comparable and to prevent hyperventilation, peak inspiratory pressure was reduced during the A/C mode so that Vetot remained in the same range as during the IMV mode. Whereas Vetot was similar in all three conditions by study design, Vemech was larger during SIMV and A/C than during IMV. Vtmech increased during SIMV and by study design was smaller during A/C than during IMV. Pe decreased during SIMV and A/C compared with IMV, and Paw was higher during A/C than during IMV or SIMV. Beat-to-beat ABP fluctuations were reduced during SIMV and A/C compared with IMV and showed a close positive correlation with Pe changes. We conclude that SIMV increases Vemech and reduces Pe compared with IMV, resulting in smaller intrathoracic and ABP fluctuations. During A/C, a substantial portion of the spontaneous respiratory effort is shifted to the ventilator, resulting in a further decrease in Pe and ABP fluctuations.