A previous report showed that methanol extracts from soil collected one year after harvesting American ginseng (Panax quinquefolius) contained activity that increased root rot caused by Ilyonectria mors-panacis. This effect was associated with suppression of the defense responses of P. quinquefolius. The activity was undetectable in soil not previously planted with ginseng, and it was hypothesized that it may be a factor in the development of ginseng replant disease (GRD). GRD can persist for 30 or more years and is associated with root rot from I. mors-panacis. A survey of activity that increases root rot was made of the soil at different times before and after commercial ginseng root harvesting. No activity that increased root rot from I. mors-panacis was detected in the soil of a first American ginseng crop over the three years from planting until prior to harvesting. After harvesting the first crop, no activity was detected during the fall or early spring, but I. mors-panacis’s ability to increase root rot was detected in the soil during late spring, when ginseng crop debris from the first crop had almost completely decayed and the soil had warmed. Activity increasing root rot from I. mors-panacis was also detected in the soil from 1 to 30 years after ginseng harvesting. These results indicate that activity in soil that increases root rot from I. mors-panacis is not detectable until after the crop has been first harvested and then can persist for many years, which is consistent with the long persistence of GRD.