Endogenous protoporphyrin IX (PpIX), which results from the oral administration of 5-aminolevulinic acid (ALA), is being investigated for its efficacy as a photosensitizing agent for photodynamic therapy (PDT). Clinical use of ALA has been associated with only mild gastrointestinal side effects. The hemodynamic effects of orally administered ALA in doses used for PDT are unknown. Six patients with a significant history of cardiac disease underwent Swan-Ganz catheterization prior to ALA administration and abdominal operation for PDT. Hemodynamic data collection began at least 1 h prior to ALA, and continued for at least 4 h subsequently, during which time no other medications were administered. When compared to measurements made prior to ALA administration, all patients displayed a significant decrease in systolic and diastolic blood pressures, pulmonary artery systolic and diastolic pressures as well as pulmonary vascular resistance. Five of the six patients also developed a decrease in systemic vascular resistance. No significant changes in pulmonary capillary wedge pressure, cardiac output or cardiac index was observed, but the mean pulse rate rose significantly. These findings cannot be explained on the basis of other cardiovascular depressants or to poor central volume status. Although no adverse sequela were appreciated as a result of the observed hemodynamic changes, this potential should be recognized in patients undergoing PDT using ALA.