How should you respond if the students frequently give answers based on guessing only?

When students guess, they could also be taught logic, probability, and statistics. So use their guestimating to teach those other 3 topics. SHOW the probability of common flaws in guessing.... and show HOW students can correctly guess in certain circumstances (such as on some multiple choice tests).
Then, instruct the students that their next quiz will need factual-specific answers to question-- so they better study! And just to keep it interesting, that you will include 3 questions on the quiz that could use some guessimating if they are unsure of the exact answer, but they will have to state their reason for their guess. Give an example statement so students learn to think and use logic in their guesses.