1. When the Ringer's solution applied to isolated frog sciatic nerve contains K+ in concentrations greater than 2 x standard, the height of the spike and of the after-potential is decreased, as is the duration of the after-potential; recovery of height and of excitability following response is delayed; degree and duration of supernormal excitability are decreased; postcathodal depression and postanodal enhancement are increased and prolonged.
2. The nerve functions just listed in general all change in the opposite direction when exposed' to increased environmental [Ca++]. (4.5–20 x standard) or decreased [K+] (0.05–0.2 x standard). The effects of decreased [Ca++] (0.20–0.25 x standard) are indeterminate.
3. When [K+] and [Ca++] are both greater than 2 x standard, whatever the ratio between the concentrations the effects characteristic of high [K+] eventually predominate. However, these effects, except for those involving spike height, are preceded by effects characteristic of high [Ca++] when this cation is present in sufficient excess.
4. When [K+] and [Ca++] are reduced to equal low levels (0.1–0.2 x standard), effects characteristic of low [K+] and high [Ca++] are obtained.
5. The experimentally determined order of ability of the environments to produce changes characteristic of high K+ (which is the reverse of the order of their ability to produce changes characteristic of high [Ca++]), is not the order of their K+ or Ca++ concentrations, nor of the ratio between these concentrations (Table II).
6. The results may be explained by the assumption that the functions investigated are all to greater or less degree controlled by (1) the [K+]/[Ca++] ratio and (2) the K+ concentration, at least when this exceeds a critical level. Control by [K+] is more effective for spike height and its recovery after stimulation than for the other functions. The special rôle of K+ is attributed to an unknown specific effect of this ion which Ca++ is unable to oppose. It is suggested that this K+ effect in general becomes marked on the frog nerve functions investigated when the K+ concentration is somewhat above 2 x standard, while the [K+]/[Ca++] ratio must be changed by a factor of 4 or more before it exerts a definite effect on these functions.
7. In standard and in modified cationic environments, nerve functions vary in the ease with which they manifest changes characteristic of high [K+] or of high [Ca++].
8. The after-potential functions are less completely controlled by the cationic environment than are the other functions investigated.