The assessment of statistical significance by Monte Carlo simulation may be costly in computer time. This paper looks at a number of ways of calculating exact Monte Carlo p-values by sequential sampling. Such p-values are shown to have properties similar to those obtained by sampling with a fixed sample size. Both standard and generalized Monte Carlo procedures are discussed and, in particular, a sequential method is proposed for dealing with situations in which values can only be conveniently generated using a Markov chain, conditioned to pass through the observed data.