Musculoskeletal pain is a common malady resulting in large treatment costs to individuals and society. A novel experimental model for myofascial pain is the intramuscular infusion of an acidic phosphate buffer solution to investigate peripheral and central mechanisms. Based on similar acid models in animals, mechanical hyperalgesia is hypothesized to occur in primary and referred pain areas but this has not been investigated in humans. Three 15-minute infusions were performed in 15 subjects (8 female) into the left anterior tibialis (ant tib) muscle belly: normal pH at 40 ml/hr (control), 5.2 pH at 40 ml/hr (acid high), and 5.2 pH at 20 ml/hr (acid low). Mechanical pressure pain thresholds (PPTs, Somedic, Sweden, 30 kPa/s) were determined at 4 locations ipsilaterally (upper and lower ant tib, ankle, and web space) and 2 contralaterally (lower ant tib and ankle). The acidic infusions produced mild to moderate pain on a 10 cm visual analog scale; with mean peak ratings of 1.50/10 (range 0.0 – 7.0) and 2.95/10 (0.7 – 9.4) for the acid low and acid high conditions, respectively. The control infusion resulted in a mean peak pain of 0.9/10 (0.0 – 3.0). Both acidic infusions resulted in decreased PPTs by 9 – 17% at the ipsilateral ant tib (primary) and ankle (referred) locations (p < 0.05). No changes in PPTs were noted at the foot web space or the contralateral locations. These results demonstrate rate dependent pain perception resulting from intramuscular infusion of an acidic phosphate buffer. Further, these preliminary findings indicate mechanical hyperalgesia occurred over the involved muscle and its referred pain region. The pain and hyperalgesia at the site of infusion is likely due to nociceptor activation and sensitization. The pain and hyperalgesia spread outside the site of infusion, i.e. referred pain, is likely associated with central mechanisms related to summation or sensitization.