This is probably a relay error. Make sure you can relay through the SmtpMail.SmtpServer either by your IP address, by your MailMessage.From address, or if you need to authenticate, check out 3.8 How do I authenticate to send an email?
If SmtpMail.SmtpServer is set to "127.0.0.1" or "localhost", and you are using the built in IIS SMTP Service, you can allow relaying for 127.0.0.1 by

• Opening the IIS Admin MMC
• Right-Clicking on the SMTP Virtual Server and selecting Properties
• On the Access tab, click the Relay BUTTON
• Grant 127.0.0.1 (or the IP address used by System.Web.Mail) to the Computers list.
• Close all dialogs
• Restarting the SMTP Service

Also, be sure to check the InnerException for any additional, helpful information.