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Notes: Background  St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy.Objectives  To assess the phototoxicity risk of SJW ingestion.Methods  Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70–77 mW cm−2) on the photoprotected lower back skin at eight 1·5-cm2 test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 µg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter.Results  The median MED and D0·025, an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm−2, range 10–56) than at baseline (median 20 J cm−2, range 14–56) (P = 0·047). Similarly, the median D0·025 at 8 h postirradiation was lower after SJW (median 22·0 J cm−2, range 15·2–53·9) than at baseline (median 33·7 J cm−2, range 22·9–136·0) (P = 0·014). The MED and D0·025 were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose–response curve was not increased after SJW ingestion.Conclusions  These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.