Biosynthesis of kasugamycin could be greatly enhanced by applying a nonnutritional stress of pH shock, that is, sequential pH changes from a neutral pH to an acidic condition and then back to the neutral condition. During the acidic period, cell growth decreased to nil. After recovery of the neutral condition, the cell growth resumed after a time lag concurrently with the biosynthesis of kasugamycin at a greatly enhanced rate compared with the control case without a pH shock. In a series of experiments performed to identify the optimal length of pH shock, four different lengths (6, 12, 24, and 48 h) of pH shock were applied. The best result was obtained when pH shock was applied for 24 h, with kasugamycin productivity approximately 7-fold higher than that of the control.