A new encapsulated liquid preparation of methoxsalen (8-MOP) and a commonly used crystalline preparation (Oxsoralen) were compared in 12 subjects. Each subject ingested 0.6 mg/kg body weight of each formulation on different days. Six subjects ingested a low-fat meal before ingestion of drug, and 6 subjects ingested a high-fat meal. Photosensitivity was tested from 1/2 to 6 h after ingestion of 8-MOP by exposure to 320-400 nm radiation (UVA) from a filtered xenon are lamp. A series of graduated doses of UVA were administered at each time point to determine the minimum phototoxic dose (MPD). Ingestion of 8-MOP and grading of erythema were conducted in a double-blind manner, and bilaterally symmetrical exposure sites were used to test each preparation. The phototoxic reaction was observed at 24, 48, and 72 h by two experienced observers who were unaware which formulation had been ingested. The two test days were separated by 48 h. The encapsulated liquid preparation induced greater photosensitivity than Oxsoralen (mean MPDs +/- SD: 7.1 +/- 4.7 vs 12.9 +/- 6.7 J/cm2, respectively; n = 12; p less than 0.05). The encapsulated liquid preparation also induced photosensitivity earlier than Oxsoralen (mean hours after ingestion to achieve peak photosensitivity +/- SD: 2.1 +/- 1.2 vs 3.9 +/- 1.6, respectively; n = 9; borderline significance). On a low-fat diet the encapsulated liquid peaked 2.5 h earlier than Oxsoralen, as well as showing the shortest and the most predictable period of photosensitivity. However, overall, the degree and time of peak photosensitivity induced by either preparation were unaffected by diet. Ingestion of the encapsulated liquid induced photosensitivity in all 12 subjects; Oxsoralen failed to sensitize 3 subjects. Side effects were similar after both preparations. A new encapsulated liquid preparation of 8-MOP may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy, and a shortened waiting period following ingestion of drug.