The progression of age-related changes in neuromuscular function was investigated in muscles from CBF-1 mice between 7 and 32 months of age. End-plate potentials (e.p.p.s) were recorded in extensor digitorum longus (e.d.l.), soleus, and diaphragm muscles after neuromuscular transmission was blocked with either (+)-tubocurarine chloride (curare) or high-Mg/low-Ca Krebs solutions. Between 10 and 31 months of age in e.d.l. and soleus but not in diaphragm, there was an increase in e.p.p. amplitude with age. In soleus this increase was approximately two-fold in curare and three-fold in high-Mg solution. Increase in e.p.p. amplitude in curarized preparations took place between 20 and 28 months of age in e.d.l. and between 28 and 31 months of age in soleus. Indirectly elicited twitch responses were used to determine the time course of age-related changes in sensitivity to Mg block. Increased resistance to block appeared between 15 and 19 months of age in both e.d.l. and soleus (in which the increase was more gradual). E.d.l. muscles from 25-month-old CFW mice also showed an increased resistance to Mg block compared to those from 7-8-month-old animals. In Mg-blocked preparations, increased quantum content (measured directly) accounted for the increased e.p.p. amplitude. Spontaneous miniature end-plate potential (m.e.p.p.) frequency in old soleus muscles was not sensitive to low-Ca/high-Mg solutions although frequency in young soleus and young and old diaphragm was significantly reduced. It is concluded that age-related changes in evoked transmitter release begin in mid life and take place more rapidly in e.d.l. than in soleus.(ABSTRACT TRUNCATED AT 250 WORDS)