We have isolated a subclonal cell line of PC12, PC12h-R, which is characterized by its rapid response to nerve growth factor (NGF) in extending its neurites. The mRNA levels of the 68-kDa neurofilament (NF-L) increased severalfold as early as 3 h after the addition of NGF, but this was not accompanied by an increase in the transcription rate. Analysis of the stabilities of 3.5- and 2.3-kilobase (kb) NF-L mRNAs using actinomycin D revealed that 2.3-kb mRNA was degraded much faster than the 3.5-kb species and that NGF apparently stabilized NF-L mRNAs. These results show that the NF-L gene can be regulated posttranscriptionally, a finding that may be important in responding to the acute demand for neurofilament syntheses.