Actinic keratoses (AKs) are traditionally treated with cryotherapy, curettage, and 5-fluorouracil (5-FU, Efudex, ICN Pharmaceuticals, Inc.), all of which are associated with adverse effects. Although photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) offers a treatment alternative, current protocols require 14 to 18 hours incubation with ALA and patients experience pain during light treatment. Fifteen patients with multiple and diffuse facial AKs applied 5-FU nightly for 5 days and underwent PDT with ALA (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) on the sixth day. ALA was applied to their entire faces and remained in contact with the skin for 30 to 45 minutes under low-intensity visible light. After removing ALA, faces received a single pass of 560- to 1200-nm intense pulsed light (VascuLight or Lumenis One, Lumenis). At 1 month and at 1 year post-treatment, 90% of treated AKs had resolved in all but one patient. Erythema resolved 7 to 10 days after treatment. Patients with multiple diffuse AKs may benefit from the application of 5-FU for 5 days followed by ALA-PDT with intense pulsed light activation.