Intravenous high-dose vitamin C is a potentially useful therapy for acute herpetic pain, but its minimum effective dose and target serum concentration have not been established. It was reported that intravenous vitamin C in a total dose of 60-75 g was effective in mitigating acute herpetic pain, while that of 15 g was not. We report two cases whose acute herpetic pain was resistant to traditional treatment but effectively relieved by intravenous high-dose vitamin C (total doses 40 and 30 g, respectively); final serum levels of vitamin C were 23.1 and 20.3 μg/ml, respectively. These findings support the notion that the effect of vitamin C on acute herpetic pain is dose-dependent, and a serum vitamin C level greater than 20 μg/ml may be needed to relieve acute herpetic pain.