Subcutaneous injection of formaldehyde into mouse hindpaw elicited pain responses consisting of licking or biting of the paw, which were observed biphasically. The first and second phases were enhanced by melatonin and melatonin, naloxone, prostglandin E2, respectively. Mice kept in the dark also exhibited hyperalgesic response. When neurotropin was injected intraperitoneally 30 min prior to those treatments, hyperalgesia was suppressed to the control level. Aspirin inhibited only the second hyperalgesic phase.